Publications by authors named "Xixun Du"

G protein-coupled receptors (GPCRs) are a class of transmembrane proteins that distribute in various organs extensively. They can regulate physiological functions such as perception, neurotransmission and endocrinology through the synergies of signaling pathways. At present, Food and Drug Administration (FDA) have approved more than 500 drugs targeting GPCRs to treat a variety of conditions, including neurological diseases, gastrointestinal diseases and tumors.

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Parkinson's disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries of recognition as a chronic disease, the exact pathogenesis of PD remains elusive. The onset and progression of PD involve multiple complex pathological processes, with dysfunctional autophagy and elevated oxidative stress serving as critical contributors.

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Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis.

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Parkinson's disease (PD) is a prevalent and advancing age-related neurodegenerative disorder, distinguished by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Iron regional deposit in SNpc is a significant pathological characteristic of PD. Brain iron homeostasis is precisely regulated by iron metabolism related proteins, whereas disorder of these proteins can damage neurons and glial cells in the brain.

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In Parkinson's disease (PD), exogenous ghrelin protects dopaminergic neurons through its receptor, growth hormone secretagogue receptor (GHSR). However, in contrast to the strikingly low levels of ghrelin, GHSR is highly expressed in the substantia nigra (SN). What role does GHSR play in dopaminergic neurons is unknown.

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Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an essential role in several neurodegenerative diseases. It was reported that increased immunostaining for ApoD of glial cells surrounding dopaminergic (DAergic) neurons was observed in the brains of Parkinson's disease (PD) patients. Although preliminary findings supported the role of ApoD in neuroprotection, its derivation and effects on the degeneration of nigral DAergic neurons are largely unknown.

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Disturbance in iron homeostasis has been described in Parkinson's disease (PD), in which iron regulatory protein 2 (IRP2) plays a crucial role. IRP2 deletion resulted in the misregulation of iron metabolism and subsequent neurodegeneration. However, growing evidence showed that the levels of IRP2 were increased in the substantia nigra (SN) in MPTP-induced PD mice.

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α-Synuclein (α-Syn) is closely related to the pathogenesis of Parkinson's disease (PD). Under pathological conditions, the conformation of α-syn changes and different forms of α-syn lead to neurotoxicity. According to Braak stages, α-syn can propagate in different brain regions, inducing neurodegeneration and corresponding clinical manifestations through abnormal aggregation of Lewy bodies (LBs) and lewy axons in different types of neurons in PD.

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OTU domain-containing protein 3 (OTUD3) knockout mice exhibited loss of nigral dopaminergic neurons and Parkinsonian symptoms. However, the underlying mechanisms are largely unknown. In this study, we observed that the inositol-requiring enzyme 1α (IRE1α)-induced endoplasmic reticulum (ER) stress was involved in this process.

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Nitric oxide (NO) is a crucial factor in regulating neuronal development. However, certain effects of NO are complex under different physiological conditions. In this study, we used differentiated neural stem cells (NSCs), which contained neural progenitor cells, neurons, astrocytes, and oligodendrocytes, to observe the physiological effects of sodium nitroprusside (SNP) on the early developmental stage of the nervous system.

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Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (DR) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions.

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Iron overload can induce oxidative stress, thereby inducing cell peroxidation. Arachidonic acid (ARA) is widely expressed in mammalian cells and esterified to membrane phospholipids. To explore the effect of iron overload on the metabolism of membrane phospholipids MES23.

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Inositol-requiring enzyme 1 α (IRE1α) is a type I transmembrane protein that resides in the endoplasmic reticulum (ER). IRE1α, which is the primary sensor of ER stress, has been proven to maintain intracellular protein homeostasis by activating X-box binding protein 1 (XBP1). Further studies have revealed novel physiological functions of the IRE1α, such as its roles in mRNA and protein degradation, inflammation, immunity, cell proliferation and cell death.

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Ghrelin contributes to the communication between the brain and gastrointestinal (GI) tract. Both decreased ghrelin levels and functional GI disorders are early events in Parkinson's disease (PD) patients and animal models. However, the reason is not clear.

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Mitochondria dysfunction has been defined as one of the hallmarks of aging-related diseases as is characterized by the destroyed integrity, abnormal distribution and size, insufficient ATP supply, increased ROS production, and subsequently damage and oxidize the proteins, lipids and nucleic acid. Mitophagy, an efficient way of removing damaged or defective mitochondria by autophagy, plays a pivotal role in maintaining the mitochondrial quantity and quality control enabling the degradation of unwanted mitochondria, and thus rescues cellular homeostasis in response to stress. Accumulating evidence demonstrates that impaired mitophagy has been associated with many neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) in a variety of patients and disease models with neural death, oxidative stress and disturbed metabolism, either as the cause or consequence.

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ATP-sensitive potassium channels (K channels), a group of vital channels that link the electrical activity of the cell membrane with cell metabolism, were discovered on the ventricular myocytes of guinea pigs by Noma using the patch-clamp technique in 1983. Subsequently, K channels have been found to be expressed in pancreatic β cells, cardiomyocytes, skeletal muscle cells, and nerve cells in the substantia nigra (SN), hippocampus, cortex, and basal ganglia. K channel openers (KCOs) diazoxide, nicorandil, minoxidil, and the K channel inhibitor glibenclamide have been shown to have anti-hypertensive, anti-myocardial ischemia, and insulin-releasing regulatory effects.

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Ferroptosis is defined as an iron-dependent, non-apoptotic cell death pathway, with specific morphological phenotypes and biochemical changes. There is a growing realization that ferroptosis has significant implications for several neurodegenerative diseases. Even though ferroptosis is different from other forms of programmed death such as apoptosis and autophagic death, they involve a number of common protein molecules.

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Accumulating evidence suggests that ATP-sensitive potassium (K ) channels play an important role in the selective degeneration of dopaminergic neurons in the substantia nigra (SN). Furthermore, the expression of the K channel subunit sulfonylurea receptor 1 (SUR1) is upregulated in the remaining nigral dopaminergic neurons in Parkinson's disease (PD). However, the mechanism underlying this selective upregulation of the SUR1 subunit and its subsequent roles in PD progression are largely unknown.

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Ghrelin was first identified as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) in 1999, with the function of stimulating the release of growth hormone (GH), while nesfatin-1 was identified in 2006. Both peptides are secreted by the same kind of endocrine cells, X/A-like cells in the stomach. Compared with ghrelin, nesfatin-1 exerts opposite effects on energy metabolism, glucose metabolism, gastrointestinal functions and regulation of blood pressure, but exerts similar effects on anti-inflammation and neuroprotection.

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Parkinson's disease (PD) is characterized by the accumulation of alpha-synuclein (α-Syn) in the substantia nigra (SN) and the degeneration of nigrostriatal dopaminergic (DAergic) neurons. Some studies have reported that the pathology of PD originates from the gastrointestinal (GI) tract, which also serves as an energy portal, and develops upward along the neural pathway to the central nervous system (CNS), including the dorsal motor nucleus of vagus (DMV), SN, and hypothalamus, which are also involved in energy metabolism control. Therefore, we discuss the alterations of nuclei that regulate energy metabolism in the development of PD.

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Iron regulatory proteins (IRPs) and iron regulatory element (IRE) systems are well known in the progression of neurodegenerative disorders by regulating iron related proteins. IRPs are also regulated by iron homeostasis. However, an increasing number of studies have suggested a close relationship between the IRPs/IRE system and non-iron-related neurodegenerative disorders.

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Aberrant α-synuclein (α-Syn) accumulation resulting from proteasome dysfunction is considered as a prominent factor to initiate and aggravate the neurodegeneration in Parkinson's disease (PD). Although the involvement of 26S proteasome in proteostasis imbalance has been widely accepted, our knowledge about the regulation of immunoproteasome function and its potential role in α-Syn pathology remains limited. Immunoproteasome abundance and proteolytic activities depend on the finely tuned assembly process, especially β-ring formation mediated by the only well-known chaperone proteasome maturation protein (POMP).

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New neurons are generated throughout life in distinct regions of the mammalian brain due to the proliferation and differentiation of neural stem cells (NSCs). Ubiquitin, a post-translational modification of cellular proteins, is an important factor in regulating neurogenesis. Deubiquitination is a biochemical process that mediates the removal of ubiquitin moieties from ubiquitin-conjugated substrates.

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We have previously established that PV neurons and Npas1 neurons are distinct neuron classes in the external globus pallidus (GPe): they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2 neurons, which are a unique subclass within the Npas1 class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes.

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